The Cysteinyl Leukotriene metabolites such as LTC4, LTD4 and LTE4 are of membrane arachidonic acid origin, and are some of the known mediators (Dahlen et al., Nature 288, 484, 1980 and Burke et al., J. Pharmacol. and Exp. Therap., 221, 235, 1983) of allergy and inflammatory born disorders such as allergic rhinitis, bronchial asthma, COPD, atopic dermatitis, urticaria, viral broncholitis, cystic fibrosis, eosinophilic gastro-enteritis, etc. CysLT1 and CysLT2 are the two receptors identified for which these mediators bind and the subsequent receptor mediated adverse responses lead to pathogenic conditions.
U.S. Pat. No. 5,856,322; U.S. Pat. No. 5,565,473; U.S. Pat. No. 5,266,568; U.S. Pat. No. 5,204,358; U.S. Pat. No. 5,104,882; U.S. Pat. No. 5,059,610; U.S. Pat. No. 5,051,427; U.S. Pat. No. 4,920,133; U.S. Pat. No. 4,920,132; EP 0315399; EP 0318093; EP 0399818; WO 1989/004303; WO 2004/043966; Chem. Rev., Article ASAP, DOI: 10.1021/cr100392s, Publication Date (Web): Apr. 28, 2011 etc discloses various leukotriene receptor antagonist.
Selective antagonists of CysLT1 receptor such as Montelukast (Singular; Merck: Bioorg. Med. Chem. Lett., 1995, 5, 283 and Progress in Medicinal chemistry Vol 38, Chapter 5, Ed, by F. D. King and A. W. Oxford, 249, 2001), Zafirlukast (Accolate: AstraZeneca: J. Med. Chem, 1990, 33, 1781) and Pranlukast (Onon® Ono: J. Med. Chem., 1988, 31, 84) have been commercialized for the treatment of seasonal allergic rhinitis, mild to moderate asthma therapy and are being evaluated for other inflammatory disorders. Since the marketed products have certain limitations for example Zafirlukast has liver microsomal binding leading to drug-drug interactions and Montelukast is being evaluated for the concern of suicidal tendencies in some subjects on prolonged use, there is a need for development of newer structures binding efficiently to the CysLT1 and showing the pharmacological activity with reduced side effect profile. Also there is a need for decreasing the steroid load on children and CysLT1 antagonists are known for their steroid sparing effect in the maintenance of Asthma.